Nephrotic syndrome, type 12

Summary

Nephrotic syndrome, type 12 (MONDO:0014817) is a disease caused by NUP93 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: NUP93 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 41

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrotic syndrome, type 12
Mondo ID	MONDO:0014817
OMIM	616892
DOID	DOID:0080387
UMLS	C4225166
MedGen	904365
GARD	0016166
Is cancer (heuristic)	no

Also known as: familial nephrotic syndrome caused by mutation in NUP93 · nephrotic syndrome, type 12 · nephrotic syndrome, type 12; NPHS12 · NPHS12 · NUP93 familial nephrotic syndrome

Data availability: 41 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › nephrotic syndrome › familial nephrotic syndrome › familial idiopathic steroid-resistant nephrotic syndrome › nephrotic syndrome, type 12

Related subtypes (13): nephrotic syndrome, type 2, focal segmental glomerulosclerosis 1, nephrotic syndrome, type 3, nephrotic syndrome, type 6, familial steroid-resistant nephrotic syndrome with sensorineural deafness, nephrotic syndrome, type 8, nephrotic syndrome, type 9, nephrotic syndrome, type 10, nephrotic syndrome, type 11, nephrotic syndrome, type 13, familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial proliferation, familial idiopathic steroid-resistant nephrotic syndrome with minimal changes, familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

41 retrieved; paginated sample, class counts are floors:

20 uncertain significance, 6 likely pathogenic, 5 benign, 4 pathogenic, 2 benign/likely benign, 2 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
224964	NM_014669.5(NUP93):c.1772G>T (p.Gly591Val)	NUP93	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
224965	NM_014669.5(NUP93):c.1886A>G (p.Tyr629Cys)	NUP93	Pathogenic/Likely pathogenic	no assertion criteria provided
224966	NM_014669.5(NUP93):c.1326del (p.Lys442fs)	NUP93	Pathogenic	no assertion criteria provided
224967	NM_014669.5(NUP93):c.1537+1G>A	NUP93	Pathogenic	no assertion criteria provided
3235149	NM_014669.5(NUP93):c.927+1G>A	NUP93	Pathogenic	criteria provided, single submitter
3768431	NM_014669.5(NUP93):c.724del (p.Ala241_Leu242insTer)	NUP93	Pathogenic	criteria provided, single submitter
2579691	NM_014669.5(NUP93):c.-14-1G>A	NUP93	Likely pathogenic	criteria provided, single submitter
3062103	NM_014669.5(NUP93):c.1733G>C (p.Arg578Pro)	NUP93	Likely pathogenic	criteria provided, single submitter
3391048	NM_014669.5(NUP93):c.1732C>T (p.Arg578Ter)	NUP93	Likely pathogenic	criteria provided, single submitter
3780053	NM_014669.5(NUP93):c.406G>T (p.Glu136Ter)	NUP93	Likely pathogenic	criteria provided, single submitter
4081566	NM_014669.5(NUP93):c.1457_1458dup (p.Cys487fs)	NUP93	Likely pathogenic	criteria provided, single submitter
599141	NM_014669.5(NUP93):c.1709T>A (p.Val570Glu)	NUP93	Likely pathogenic	no assertion criteria provided
224968	NM_014669.5(NUP93):c.1162C>T (p.Arg388Trp)	NUP93	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
499268	NM_014669.5(NUP93):c.1882_1899del (p.Leu628_Lys633del)	NUP93	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3064817	NM_001719.3(BMP7):c.866G>A (p.Arg289His)	BMP7	Uncertain significance	criteria provided, single submitter
1310508	NM_014669.5(NUP93):c.910C>T (p.Pro304Ser)	NUP93	Uncertain significance	criteria provided, multiple submitters, no conflicts
1321681	NM_014669.5(NUP93):c.1985G>A (p.Arg662Lys)	NUP93	Uncertain significance	criteria provided, multiple submitters, no conflicts
1344863	NM_014669.5(NUP93):c.2017C>T (p.Arg673Trp)	NUP93	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442155	NM_014669.5(NUP93):c.1574G>A (p.Arg525Gln)	NUP93	Uncertain significance	criteria provided, multiple submitters, no conflicts
2585173	NM_014669.5(NUP93):c.2141T>C (p.Ile714Thr)	NUP93	Uncertain significance	criteria provided, single submitter
2681755	NM_014669.5(NUP93):c.1573C>T (p.Arg525Trp)	NUP93	Uncertain significance	criteria provided, single submitter
2681757	NM_014669.5(NUP93):c.1899G>A (p.Lys633=)	NUP93	Uncertain significance	criteria provided, single submitter
3023299	NM_014669.5(NUP93):c.1126C>T (p.Arg376Cys)	NUP93	Uncertain significance	criteria provided, multiple submitters, no conflicts
3234055	NM_014669.5(NUP93):c.2065T>A (p.Phe689Ile)	NUP93	Uncertain significance	criteria provided, single submitter
3384680	NM_014669.5(NUP93):c.1912G>A (p.Val638Ile)	NUP93	Uncertain significance	no assertion criteria provided
3764796	NM_014669.5(NUP93):c.1085_1085+2dup	NUP93	Uncertain significance	criteria provided, single submitter
4292389	NM_014669.5(NUP93):c.2018+362G>C	NUP93	Uncertain significance	criteria provided, single submitter
4292509	NM_014669.5(NUP93):c.795-303A>C	NUP93	Uncertain significance	criteria provided, single submitter
4292918	NM_014669.5(NUP93):c.949C>T (p.Pro317Ser)	NUP93	Uncertain significance	criteria provided, single submitter
635548	NM_014669.5(NUP93):c.1837G>C (p.Ala613Pro)	NUP93	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
NUP93	Definitive	Autosomal recessive	nephrotic syndrome, type 12	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NUP93	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NUP93	HGNC:28958	ENSG00000102900	Q8N1F7	Nuclear pore complex protein Nup93	gencc,clinvar
BMP7	HGNC:1074	ENSG00000101144	P18075	Bone morphogenetic protein 7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NUP93	Nuclear pore complex protein Nup93	Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance.
BMP7	Bone morphogenetic protein 7	Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NUP93	Other/Unknown	no		Nucleoporin_int_Nup93/Nic96
BMP7	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
ganglionic eminence	1
left lobe of thyroid gland	1
endometrium epithelium	1
pigmented layer of retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NUP93	285	ubiquitous	marker	ventricular zone, ganglionic eminence, left lobe of thyroid gland
BMP7	243	broad	marker	pigmented layer of retina, ventricular zone, endometrium epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMP7	3,134
NUP93	3,031

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NUP93	Q8N1F7	7
BMP7	P18075	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 38. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transcriptional regulation of brown and beige adipocyte differentiation	1	571.0×	0.013	BMP7
Postmitotic nuclear pore complex (NPC) reformation	1	203.9×	0.013	NUP93
IPs transport between nucleus and cytosol	1	190.3×	0.013	NUP93
IP3 and IP4 transport between cytosol and nucleus	1	190.3×	0.013	NUP93
IP6 and IP7 transport between cytosol and nucleus	1	190.3×	0.013	NUP93
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	190.3×	0.013	BMP7
Transport of Ribonucleoproteins into the Host Nucleus	1	178.4×	0.013	NUP93
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	178.4×	0.013	NUP93
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	178.4×	0.013	NUP93
NEP/NS2 Interacts with the Cellular Export Machinery	1	173.0×	0.013	NUP93
Elastic fibre formation	1	167.9×	0.013	BMP7
Nuclear import of Rev protein	1	167.9×	0.013	NUP93
Vpr-mediated nuclear import of PICs	1	167.9×	0.013	NUP93
Transport of the SLBP independent Mature mRNA	1	163.1×	0.013	NUP93
SUMOylation of SUMOylation proteins	1	163.1×	0.013	NUP93
Transport of the SLBP Dependant Mature mRNA	1	158.6×	0.013	NUP93
Rev-mediated nuclear export of HIV RNA	1	158.6×	0.013	NUP93
Molecules associated with elastic fibres	1	154.3×	0.013	BMP7
Nuclear Pore Complex (NPC) Disassembly	1	154.3×	0.013	NUP93
SUMOylation of ubiquitinylation proteins	1	146.4×	0.013	NUP93
NS1 Mediated Effects on Host Pathways	1	142.8×	0.013	NUP93
Transport of Mature mRNA Derived from an Intronless Transcript	1	135.9×	0.013	NUP93
Viral Messenger RNA Synthesis	1	129.8×	0.013	NUP93
SUMOylation of DNA replication proteins	1	124.1×	0.013	NUP93
SUMOylation of RNA binding proteins	1	119.0×	0.013	NUP93
snRNP Assembly	1	105.7×	0.014	NUP93
tRNA processing in the nucleus	1	98.5×	0.014	NUP93
SUMOylation of chromatin organization proteins	1	79.3×	0.016	NUP93
Adipogenesis	1	78.2×	0.016	BMP7
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	76.1×	0.016	NUP93

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of SMAD protein signal transduction	2	383.0×	5e-04	NUP93, BMP7
negative regulation of mesenchymal cell apoptotic process involved in nephron morphogenesis	1	8426.0×	0.002	BMP7
mesenchymal cell apoptotic process involved in nephron morphogenesis	1	8426.0×	0.002	BMP7
negative regulation of glomerular mesangial cell proliferation	1	4213.0×	0.002	BMP7
nephrogenic mesenchyme morphogenesis	1	4213.0×	0.002	BMP7
negative regulation of striated muscle cell apoptotic process	1	2808.7×	0.002	BMP7
neural fold elevation formation	1	2808.7×	0.002	BMP7
monocyte aggregation	1	2808.7×	0.002	BMP7
metanephric mesenchyme morphogenesis	1	2808.7×	0.002	BMP7
metanephric mesenchymal cell proliferation involved in metanephros development	1	2808.7×	0.002	BMP7
positive regulation of hyaluranon cable assembly	1	2808.7×	0.002	BMP7
positive regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis	1	2808.7×	0.002	BMP7
negative regulation of prostatic bud formation	1	2106.5×	0.003	BMP7
allantois development	1	2106.5×	0.003	BMP7
regulation of branching involved in prostate gland morphogenesis	1	1685.2×	0.003	BMP7
regulation of removal of superoxide radicals	1	1404.3×	0.003	BMP7
negative regulation of mitotic nuclear division	1	1203.7×	0.003	BMP7
mesenchyme development	1	1203.7×	0.003	BMP7
pericardium morphogenesis	1	1053.2×	0.003	BMP7
ameloblast differentiation	1	1053.2×	0.003	BMP7
mesenchymal cell differentiation	1	1053.2×	0.003	BMP7
chorio-allantoic fusion	1	1053.2×	0.003	BMP7
positive regulation of epithelial cell differentiation	1	936.2×	0.003	BMP7
heart trabecula morphogenesis	1	936.2×	0.003	BMP7
nuclear pore complex assembly	1	842.6×	0.004	NUP93
mesonephros development	1	766.0×	0.004	BMP7
embryonic skeletal joint morphogenesis	1	766.0×	0.004	BMP7
endocardial cushion formation	1	702.2×	0.004	BMP7
branching involved in salivary gland morphogenesis	1	702.2×	0.004	BMP7
positive regulation of heterotypic cell-cell adhesion	1	648.1×	0.004	BMP7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NUP93	1	2
BMP7	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	NUP93

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
NUP93	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	NUP93

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	NUP93
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BMP7

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BMP7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.